Three years ago we proposed to study in detail a theory developed by Voorhees et al that the increased cell proliferation and glycogen accumulation in the psoriatic lesional epidermis was due to a combination of a low cyclic AMP and a high cyclic GMP. Our investigations thus far have not confirmed the findings of a low cyclic AMP content within the psoriatic lesional epidermis. In fact, when the skin samples were microdissected to give pure epidermal specimens, we found that the cyclic AMP level was 20-25% higher in the lesion than in the uninvolved epidermis. In addition, we found that the major abnormality in the psoriatic lesion is a profound inability to respond to catecholamines. We, therefore, propose to complete our work on the original concept by finishing our investigation of specific phosphodiesterases and by measuring the cyclic GMP levels within the psoriatic lesion. If cyclic GMP is found to be elevated, further work on elucidating the cause for this would be justified. If the cyclic GMP content is not found to be different from the uninvolved, we intend to investigate the abnormality in the epidermal cell which leads to the lack of responsiveness. We believe this lack of responsiveness may be a general phenomena in epidermis which has been stimulated to hyperproliferation. Knowledge of this mechanism would therefore be of intense interest in wound healing and cancer, as well as in psoriasis.